Differential microRNA profile underlies the divergent healing responses in skin and oral mucosal wounds

Abstract

Oral mucosal wounds heal faster than skin wounds, yet the role of microRNAs in this differential healing has never been examined. To delineate the role of microRNAs in this site-specific injury response, we first compared the microRNAome of uninjured skin and oral mucosa in mice. A total of 53 tissue-specific microRNAs for skin and oral mucosa epithelium were identified. The most striking difference was the high abundance of miR-10a/b in skin (accounting for 21.10% of the skin microRNAome) as compared to their low expression in oral mucosa (2.87%). We further examined the dynamic changes of microRNAome throughout the time course of skin and oral mucosal wound healing. More differentially expressed microRNAs were identified in skin wounds than oral wounds (200 and 33, respectively). More specifically, miR-10a/b was significantly down-regulated in skin but not oral wounds. In contrast, up-regulation of miR-21 was observed in both skin and oral wounds. The therapeutic potential of miR-10b and miR-21 in accelerating wound closure was demonstrated in in vitro assays and in a murine skin wound model. Thus, we provided the first site-specific microRNA profile of skin and oral mucosal wound healing, and demonstrate the feasibility of a microRNA-based therapy for promoting wound closure.

Site-Specific Expression Pattern of PIWI-Interacting RNA in Skin and Oral Mucosal Wound Healing

“…One of our important observations is that more piRNA genes were differentially expressed in skin wounds than in oral mucosal wounds. This is in agreement with our previous observations showing that nearly twice as many protein-coding genes and six times as many microRNA genes are differentially expressed in the skin wounds than in mucosal wounds [2,3]. Collectively, these observations imply that, as compared to the skin, the oral mucosa has an intrinsic genetic/epigenetic controlling program that makes it be highly adaptable to the accelerated healing upon injury.…”

“…In this study, we present the first tissue-specific piRNA profiles in corresponding skin and oral mucosal wounds. Together with our previous study that established the tissue-specific transcriptome and microRNAome of matching skin and mucosal wounds [2,3], we demonstrated striking differences in the transcribed genome (transcriptome, microRNAome, and piRNAome) of oral mucosal and skin wounds. Along with studies by others [4,29], our results suggest that the intrinsic differences in the genetic and epigenetic responses to injury in the skin and mucosa contribute to the divergent wound healing outcomes.…”

“…The expression of piRNA genes in the normal murine uninjured skin and oral mucosal epithelium (baseline) was explored by re-analyzing of our previous small-RNA seq data [3], and mapping to the piRNA database. A total of 20,862,850 and 3,769,588 sequence reads were mapped to 1084 and 1103 unique piRNAs for skin and oral mucosa, respectively.…”

“…Oral mucosal wound healing has long been considered an optimal wound resolution and is characterized by rapid and scarless healing. Recent comparative studies focusing on differential molecular characterization of the skin and oral mucosa have revealed that the intrinsic molecular differences in skin and oral mucosa contribute to the divergent wound healing outcomes [2][3][4]. This novel approach defines critical molecular regulators involved in accelerated wound healing and allows the harnessing of regenerative healing capabilities in oral mucosa to treat deficient healing processes.…”

Differential Expression and Function of Bicellular Tight Junctions in Skin and Oral Wound Healing

“…The skin and oral mucosa share some histological similarities, yet oral mucosal wounds heal with faster re-epithelialization, decreased inflammation, a refined angiogenic response, and minimal scarring [3][4][5][6][7]. Our most recent studies demonstrate that microRNA 10a/b, 21, and 31 may be partially responsible for the different outcomes observed in skin and oral wound healing [27,28]. Although these findings have been well characterized, the precise mechanisms behind the more regenerative response to injury in the oral cavity is still being elucidated.…”